Fluorinated amino acids and their derived peptides have been widely employed as potential pharmaceutical agents due to their broad biological properties, which include enzyme inhibitors, receptor antagonist and lipophilicity enhancing agents. While much development has focused on preparation of various fluorinated analogues of natural and non-proteinogenic amino acids, asymmetric synthesis of γ-fluoro-α-amino acids still remains a challenge. In this regard, stereoselective incorporations of the γ-F-containing side chain have been mostly executed by either a chiral auxiliary-directed diastereoselective alkylation or a chiral phase transfer-catalyzed alkylation of protected amino acid precursors.
The instant invention describes a novel stereoselective preparation of fluoroleucine alkyl esters which comprises an efficient throughput process.